Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
completion around

Description

Summary

The purpose of this study is to establish the recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of ORIC-114 as a Single Agent or in Combination with Chemotherapy when administered to patients with advanced solid tumors harboring an EGFR or HER2 alteration.

Official Title

An Open-Label, Phase 1/2 Study of ORIC-114 as a Single Agent or in Combination With Chemotherapy, in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

Details

ORIC-114 is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor designed to target EGFR and HER2 alterations, making it a promising therapeutic candidate for development in patients whose tumors harbor these alterations, including those with CNS metastases.

This is a first-in-human, open-label, single arm, multicenter, dose escalation study of ORIC-114 as a single agent (Part I), followed by dose optimization (Part II) to establish the recommended phase 2 dose (RP2D) and antitumor activity of ORIC-114 in patients with advanced solid tumors harboring an EGFR or HER2 alteration who have exhausted available treatment options. After the optimal RP2D has been determined, Phase 2 will be initiated via protocol amendment to add one or more expansion cohorts of patients with specific tumor types, treatment history, and/or expression of a specific biomarker to evaluate the antitumor activity of ORIC-114.

After completion of Part I dose escalation, Part III, a dose escalation study of ORIC-114 in combination with chemotherapy (carboplatin-pemetrexed) may be initiated to establish the RP2D and/or MTD and antitumor activity for the combination.

Keywords

Solid Tumors, EGFR exon 20 insertion mutation, Atypical EGFR mutation, HER2 exon 20 insertion mutation, HER2 amplification/overexpression, NSCLC, Neoplasms, Carboplatin, Pemetrexed, ORIC-114, Chemotherapy drug

Eligibility

You can join if…

Open to people ages 18 years and up

  • Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented EGFR or HER2 exon 20 insertion mutation or atypical EGFR mutation as determined by any nucleic acid-based diagnostic testing method, or HER2 amplification/overexpression as determined by an immunohistochemistry (IHC) or an in situ hybridization (ISH) test
  • Previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable
    • In Parts I and II NSCLC patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum-based chemotherapy is contraindicated
    • Part II Dose Optimization Cohort IIA: patients must either be naïve to an EGFR exon 20 targeted agent or only have received prior amivantamab, Cohort IIB: patients must be naïve to a HER2 targeted TKI, Cohort IIC: patients may have received a prior EGFR TKI
    • In Part III, patients may have received any number of prior treatments
  • Agreement and ability to undergo pretreatment biopsy
  • Measurable disease according to RECIST 1.1
  • CNS involvement, which is either previously treated and controlled, or untreated and asymptomatic
  • ECOG performance status of 0 or 1
  • Adequate organ function

You CAN'T join if...

  • Known EGFR T790M mutation
  • Leptomeningeal disease and spinal cord compression

    -- Except if LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the Investigator; the subject must be free of neurological symptoms of LMD

  • History of class III or IV congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months
  • Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
  • Known, symptomatic human immunodeficiency virus (HIV) infection
  • Known active infection requiring treatment or history of hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients positive for HBsAg but normal HBV DNA level are allowed.
  • Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes
  • Any other concurrent serious uncontrolled medical, psychological, or addictive conditions

Locations

  • UCSF accepting new patients
    San Francisco California 94122 United States
  • City of Hope not yet accepting patients
    Duarte California 91010 United States
  • Next Oncology accepting new patients
    Fairfax Virginia 22031 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
ORIC Pharmaceuticals
ID
NCT05315700
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 280 study participants
Last Updated